Background: Previous studies have found a link between a low DNA repair capacity (DRC) level and increased cancer risk. Our aim was to assess the statistical association of DRC level and breast cancer (BC) using a case–control epidemiological study in a Hispanic community. Methods: We conducted a comparative observational study to assess the validity of DRC in detecting BC in 824 women throughout Puerto Rico. Over a 6-year period, we compared 285 women newly diagnosed with BC to 539 without BC. DRC levels were measured in lymphocytes by means of a host-cell reactivation assay. We assessed the sensitivity, specificity, and association using the receiver operating characteristic curve analysis. Multiple logistic regression-adjusted odds ratios were estimated with 95% confidence level to measure the strength of the association of DRC and BC after adjusting for all confounders simultaneously. Results: Compared to women without cancer, women with BC showed an average decrease of 60% in their DRC levels (p < 0.001). Validity of the association of DRC as a measure of BC risk showed a sensitivity of 83.2% and specificity of 77.6% (p < 0.0001). Conclusions: Our results support the usefulness of DRC level as a measure of BC risk. Additional studies in other populations are needed to further verify its usefulness.